Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined with Antidepressant Pharmacotherapy
Published Date:Jan 2011
Source:Arch Gen Psychiatry. 68(1):51-60.
Keywords:Activities Of Daily Living
Aged, 80 And Over
Depressive Disorder, Major
Drug Therapy, Combination
Pubmed Central ID:PMC3076045
Funding:UL1 TR000005/TR/NCATS NIH HHS/United States
AG005133-24/AG/NIA NIH HHS/United States
R01 MH083660/MH/NIMH NIH HHS/United States
R01 AG022462/AG/NIA NIH HHS/United States
P50 AG005133-24/AG/NIA NIH HHS/United States
R01 MH037869-25/MH/NIMH NIH HHS/United States
R01 MH043823/MH/NIMH NIH HHS/United States
R01 MH043832-16A1/MH/NIMH NIH HHS/United States
R01 MH072947-05S1/MH/NIMH NIH HHS/United States
P30 MH071944/MH/NIMH NIH HHS/United States
R01MH072947/MH/NIMH NIH HHS/United States
AG030653/AG/NIA NIH HHS/United States
R01 AG030653-03/AG/NIA NIH HHS/United States
MH072947-05S1/MH/NIMH NIH HHS/United States
P50 AG005133/AG/NIA NIH HHS/United States
K01 EB009724/EB/NIBIB NIH HHS/United States
P50 AG05133/AG/NIA NIH HHS/United States
R01 MH072947/MH/NIMH NIH HHS/United States
KL2 TR000146/TR/NCATS NIH HHS/United States
R01 AG030653/AG/NIA NIH HHS/United States
R01 MH037869/MH/NIMH NIH HHS/United States
P30 MH071944-05/MH/NIMH NIH HHS/United States
R49 CE001495/CE/NCIPC CDC HHS/United States
R21 AG033387/AG/NIA NIH HHS/United States
R01 MH043832/MH/NIMH NIH HHS/United States
Cognitive impairment in late-life depression is a core feature of the illness.
to test whether donepezil + antidepressant is superior to placebo + antidepressant in (1) improving cognitive performance and instrumental activities of daily living and (2) reducing recurrences of depression over two years of maintenance treatment.
Randomized, double-blind, placebo controlled maintenance trial.
Main Outcome Measures
global neuropsychological performance, cognitive instrumental ADL, and recurrent depression.
Donepezil + antidepressant temporarily improved global cognition (treatment by time interaction F = 3.78, df = 2, 126, p = .03), but effect sizes were small (Cohen’s d = 0.27: group difference at 1 year). A marginal benefit to cognitive instrumental ADL was also observed (treatment by time interaction; F = 2.94; df = 2, 137, p = 0.06). The donepezil group was more likely to experience recurrent major depression: 35% [95% CI: 24%, 46%] versus 19% [95% CI: 9%, 29%] (log rank chi squared = 3.97, p = .05); hazard ratio = 2.09 [95% CI: 1.00, 4.41]. Post-hoc subgroup analyses showed that, of 57 participants with mild cognitive impairment, 3/30 on donepezil (10%; 95% CI: 0, 21%) and 9/27 on placebo (33%; 95% CI: 16%, 51%) converted to dementia over two years (Fisher exact p = 0.05). The MCI subgroup had a 44 percent recurrence rate of major depression on donepezil verses 12% on placebo (LR=4.91, p=.03). The subgroup with normal cognition (n = 73) showed no benefit on donepezil or increase in recurrence of major depression.
Whether ChEI should be used as augmentation in the maintenance treatment of late-life depression depends upon a careful weighing of risks and benefits in those with MCI. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to MCI/dementia or recurrence of depression.
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